Neurotransmitter interactions in schizophrenia–therapeutic implications
Abstract
The search for new and improved antipsychotic agents has escalated during the past five years. The era of searching for non-toxic copies of clozapine has been followed by several different lines of research, some of which pursue the traditional dopamine track, although at a higher level of sophistication, whereas others focus on other neurotransmitters, such as serotonin and glutamate. Emerging knowledge about the interactions between different neurotransmitters in complex neurocircuits opens up possibilities for achieving antipsychotic activity by interfering with many different neurotransmitters. Most intriguing is the finding in animal experimental models, indicating that it should be possible to alleviate psychotic conditions by stabilizing rather than paralyzing neurocircuits, thus avoiding the risk of motor and mental side effects of the currently used drugs. Among these new classes dopaminergic stabilizers and 5-HT2A receptor antagonists seem to offer most promise at present. In a longer perspective, drugs interfering with glutamate function via different mechanisms may also turn out to be useful, especially in the control of negative symptoms.
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Glutamatergic frontal neurons influence dopaminergic neurotransmission in the VS via GABAergic neurons.
“with studies reporting an influence of glutamatergic frontal neurons on dopaminergic neurotransmission in the VS via GABAergic neurons (Carlsson et al. 1999)”
From Circuit Mechanisms of Reward, Anhedonia, and Depression (2019) · cites this paper as Carlsson et al. 1999
Cites
Functional architecture of basal ganglia circuits: neural substrates of parallel processing
Alexander, G. E., & Crutcher, M. D. (1990) · Trends in Neurosciences · doi:10.1016/0166-2236(90)90107-l · Cited by 4,131 · see citing works
Psychopharmacology: The Fourth Generation of Progress
Bloom, F. E., & Kupfer, D. J. (1995) · Medical Entomology and Zoology · Cited by 2,985 · see citing works
Laruelle, M., Abi-Dargham, A., van Dyck, C. H., Gil, R., D'Souza, C. D., Erdos, J., McCance, E., Rosenblatt, W., Fingado, C., Zoghbi, S. S., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.17.9235 · Cited by 1,291 · see citing works
Breier, A., Su, T.-P., Saunders, R., Carson, R. E., Kolachana, B. S., de Bartolomeis, A., Weinberger, D. R., Weisenfeld, N., Malhotra, A. K., Eckelman, W. C., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2569 · Cited by 1,154 · see citing works
Carlsson, M. L., & Carlsson, A. (1990) · Trends in Neurosciences · doi:10.1016/0166-2236(90)90108-m · Cited by 1,086 · see citing works
Self-citationReversal of Phencyclidine Effects by a Group II Metabotropic Glutamate Receptor Agonist in Rats
Moghaddam, B., & Adams, B. W. (1998) · Science · doi:10.1126/science.281.5381.1349 · Cited by 1,006 · see citing works
The current status of the dopamine hypothesis of schizophrenia
Carlsson, A. C. (1988) · Neuropsychopharmacology · doi:10.1016/0893-133x(88)90012-7 · Cited by 959 · see citing works
Self-citationIncreased striatal dopamine transmission in schizophrenia: confirmation in a second cohort.
Abi-Dargham, A., Gil, R. B., Krystal, J., Baldwin, R., Seibyl, J., Bowers, M., van Dyck, C., Charney, D., Innis, R., & Laruelle, M. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.6.761 · Cited by 860 · see citing works
Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia
Kim, J. S., Kornhuber, H. H., Schmid‐Burgk, W., & Holzmüller, B. (1980) · Neuroscience Letters · doi:10.1016/0304-3940(80)90178-0 · Cited by 694 · see citing works
The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice
Carlsson, M., & Carlsson, A. (1989) · Journal of Neural Transmission · doi:10.1007/bf01258633 · Cited by 423 · see citing works
Self-citationThe role of 5-HT2A receptors in antipsychotic activity
Schmidt, C. J., Sorensen, S. M., Kenne, J. H., Carr, A. A., & Palfreyman, M. G. (1995) · Life Sciences · doi:10.1016/0024-3205(95)00210-w · Cited by 215 · see citing works
Hietala, J. A. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950020040004 · Cited by 176 · see citing works
Presynaptic dopaminergic function in the striatum of schizophrenic patients
Dao-Castellana, M. H., Martinot, M. P., Hantraye, P., Attar-Levy, D., Rémy, P., Crouzel, C., Eric Artiges, A., Féline, A., Syrota, A., & Martinot, J. (1997) · Schizophrenia Research · doi:10.1016/s0920-9964(96)00102-8 · Cited by 160 · see citing works
Miller, D. W., & Abercrombie, E. D. (1996) · Brain Research Bulletin · doi:10.1016/0361-9230(95)02144-2 · Cited by 146 · see citing works
Carlsson, M. L., & Svensson, A. I. (1990) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(90)90123-y · Cited by 123 · see citing works
Self-citationMuscimol: GABA agonist therapy in schizophrenia
Tamminga, C. A., Crayton, J. W., & Chase, T. N. (1978) · American Journal of Psychiatry · doi:10.1176/ajp.135.6.746 · Cited by 115 · see citing works
Sonesson, C., Lin, C., Hansson, L. O., et al. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00043a013 · Cited by 113 · see citing works
Lahti, A. C., Weiler, M. A., Corey, P. K., et al. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00030-9 · Cited by 104 · see citing works
Agren, H., Reibring, L., Hartvig, P., Tedroff, J., Bjurling, P., Hörnfeldt, K., Andersson, Y., Lundqvist, H., & Långström, B. (1991) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1991.tb05574.x · Cited by 97 · see citing works
Martin, P., Waters, N., Schmidt, C. J., Carlsson, A., & Carlsson, M. L. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050064 · Cited by 86 · see citing works
Self-citationCarlsson, M. L. (1995) · Journal of Neural Transmission · doi:10.1007/bf01276460 · Cited by 86 · see citing works
Self-citationCarlsson, M. L., Martin, P., Nilsson, M., Sorensen, S. M., Carlsson, A., Waters, N., & Waters, N. (1999) · Journal of Neural Transmission · doi:10.1007/s007020050144 · Cited by 78 · see citing works
Self-citationSvensson, K. A., Hjorth, S., Clark, D. T., et al. (1986) · Journal of Neural Transmission · doi:10.1007/bf01249608 · Cited by 43 · see citing works
Hansson, L. O., Waters, N., Holm, S., et al. (1995) · Journal of Medicinal Chemistry · doi:10.1021/jm00016a015 · Cited by 33 · see citing works
Self-citationHansson, L. ‐., Waters, N., Winblad, B. G., et al. (1994) · Journal of Neural Transmission · doi:10.1007/bf01276538 · Cited by 29 · see citing works
Self-citationWaters, N., Lundgren, C., Hansson, L. ‐., & Carlsson, M. L. (1996) · Journal of Neural Transmission · doi:10.1007/bf01292621 · Cited by 25 · see citing works
Self-citationCarlsson, M. L., & Svensson, A. I. (1990) · Amino Acids · doi:10.1007/978-94-011-2262-7_56 · Cited by 9 · see citing works
Self-citationLindström, L. H., Gefvert, O., Hagberg, G. E., et al. (1998) · Schizophrenia Research · doi:10.1016/s0920-9964(97)88535-0 · Cited by 9 · see citing works
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Kapur, S., & Seeman, P. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.3.360 · Cited by 1,140 · see citing works
Dopamine as a Prolactin (PRL) Inhibitor
Ben-Jonathan, N., & Hnasko, R. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.6.0451 · Cited by 983 · see citing works
The Computational Anatomy of Psychosis
Adams, R. A., Stephan, K. E., Brown, H. R., Frith, C. D., & Friston, K. J. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00047 · Cited by 850 · see citing works
Dysfunction of ventral striatal reward prediction in schizophrenia
Juckel, G., Schlagenhauf, F., Koslowski, M., Wüstenberg, T., Villringer, A., Knutson, B., Wrase, J., & Heinz, A. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.07.051 · Cited by 578 · see citing works
Glutamate, Dopamine, and Schizophrenia: From Pathophysiology to Treatment
LARUELLE, M., KEGELES, L. S., & ABI‐DARGHAM, A. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1300.063 · Cited by 437 · see citing works
Moghaddam, B. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01362-2 · Cited by 392 · see citing works
Baldessarini, R. J. (2013) · doi:10.1007/978-1-4614-3710-9 · Cited by 365 · see citing works
Meyer, U., Yee, B. K., & Feldon, J. (2007) · The Neuroscientist · doi:10.1177/1073858406296401 · Cited by 303 · see citing works
Altered excitatory-inhibitory balance in the NMDA-hypofunction model of schizophrenia
Kehrer, C. (2008) · Frontiers in Molecular Neuroscience · doi:10.3389/neuro.02.006.2008 · Cited by 287 · see citing works
Functional Dysconnectivity of Corticostriatal Circuitry as a Risk Phenotype for Psychosis
Fornito, A., Harrison, B. J., Goodby, E., Dean, A., Ooi, C., Nathan, P. J., Lennox, B. R., Jones, P. B., Suckling, J., & Bullmore, E. T. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.1976 · Cited by 279 · see citing works
Circuit Mechanisms of Reward, Anhedonia, and Depression
Höflich, A., Michenthaler, P., Kasper, S., & Lanzenberger, R. (2019) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyy081 · Cited by 253 · see citing works
Antioxidants as potential therapeutics for neuropsychiatric disorders
Pandya, C. D., Howell, K. R., & Pillai, A. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.10.017 · Cited by 222 · see citing works
Left temporal lobe structural and functional abnormality underlying auditory hallucinations
Hugdahl, K. (2009) · Frontiers in Neuroscience · doi:10.3389/neuro.01.001.2009 · Cited by 112 · see citing works
“A glutamate hypothesis has been proposed for schizophrenia (see Carlsson et al., 1999; Kehrer et al., 2008; Olney and Farber, 1995), suggesting that glutamate function in addition to dopamine function may be altered in patients with schizophrenia.”
BackgroundGleich, T., Deserno, L., Lorenz, R. C., Boehme, R., Pankow, A., Buchert, R., Kuhn, S., Heinz, A., Schlagenhauf, F., & Gallinat, J. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0329-15.2015 · Cited by 62 · see citing works
van Berckel, B. N. M., Kegeles, L. S., Waterhouse, R., Guo, N., Hwang, D.-R., Huang, Y., Narendran, R., Van Heertum, R., & Laruelle, M. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300902 · Cited by 43 · see citing works
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Zugno, A. I., Oliveira, M. B., Mastella, G. A., Heylmann, A. S. A., Canever, L., Pacheco, F. D., Damazio, L. S., Citadin, S. A., de Lucca, L. A., Simões, L. R., et al. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.02.010 · Cited by 6 · see citing works
- Authors
- Carlsson, A., Waters, N., & Carlsson, M. L.
- Affiliations
- University of Gothenburg (SE)
- Corresponding author
- Carlsson, Arvid
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 1999-11
- Volume
- 46
- Issue
- 10
- Pages
- 1388-1395
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1978196348
- Cited by
- 298
- References
- 28
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 7 · 2016: 14 · 2015: 11 · 2014: 13 · 2013: 16 · 2012: 17
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- schizophrenia, neurotransmitter interactions, antipsychotic drugs, dopamine, serotonin, glutamate, 5-HT2A receptor antagonist, negative symptoms, neural circuits, clozapine
- MeSH terms
- Animals, Disease Models, Animal, Dopamine, Humans, Interneurons, Schizophrenia, Serotonin, Thalamus, Antipsychotic Agents, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Receptors, GABA, Neuroprotective Agents, Glutamic Acid
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